1. Field of the Invention
The present invention relates to an electrochemical biosensor and a biosensor measuring device.
2. Description of the Related Art
For the diagnosis and prophylaxis of diabetes mellitus, the importance of periodic monitoring of blood glucose levels has been increasingly emphasized. Nowadays, strip-type biosensors designed for hand-held reading devices allow individuals to readily monitor glucose levels in blood.
A large number of commercialized biosensors measure blood glucose present in blood samples using an electrochemical technique. The principle of the electrochemical technique is based on the following Reaction 1.Glucose+GOx-FAD→gluconic acid+GOx-FADH2 GOx-FADH2+Mox→GOx-FAD+Mred  [Reaction 1]
wherein, GOx represents glucose oxidase; GOx-FAD and GOx-FADH2 respectively represent an oxidized and a reduced state of glucose-associated FAD (flavin adenine dinucleotide), a cofactor required for the catalyst of glucose oxidase; and Mox and Mred denote an oxidized and a reduced state of an electron transfer mediator, respectively.
The electrochemical biosensor uses organic electron transfer materials, such as ferrocenes or their derivatives, quinines or their derivatives, organic or inorganic materials containing transition metals (hexaamine ruthenium, polymer containing osmium, potassium ferricyamide and the like), organic conducting salts, and viologens, as electron transfer mediators.
The principle of measuring blood glucose by the biosensor is as follows.
glucose in blood is oxidized to gluconic acid by the catalysis of the glucose oxidase, with the cofactor FAD reduced to FADH2. Then, the reduced cofactor FADH2 transfers electrons to the mediator, so that FADH2 returns to its oxidized state; that is, FAD and the mediator are reduced. The reduced mediator is diffused to the surface of the electrodes. The series of reaction cycles is driven by the anodic potential applied at the working electrode, and the redox current proportional to the level of glucose is measured.
Compared to biosensors based on colorimetry, the electrochemical biosensors (e.g., based on electrochemistry) has the advantages of being not influenced by oxygen and allowing the use of samples, even if cloudy, without pretreatment thereof.
Although this electrochemical biosensor is generally conveniently used to monitor and control the amount of blood glucose, its accuracy is greatly dependent on deviations according to each mass-production lot in which the biosensors are produced. In order to eliminate this deviation, most of the commercialized biosensors are designed such that a user directly inputs calibration curve information, which is predetermined at the factory, into a measuring device capable of reading the biosensor. However, this method causes the user inconvenience and causes the user to make an input error, thus inaccurate results can be acquired.
In order to solve such a problem, a method that can adjust the resistance of each electrode such that production information for each lot is stored at a location at which contact of the electrode of a sensor is made (US20060144704A1), a method in which a conductor is printed in a bar code type (U.S. Pat. No. 6,814,844), a method in which a connection to a resistor bank is made (WO2007011569A2), and a method that reads information by varying resistance through adjustment of length or thickness of each electrode (US20050279647A1) have been proposed. The methods proposed for the electrochemical biosensors are all based on a technique capable of reading electrical variation. Furthermore, a method that discriminates production lot information by reading the resistivity of a conductor marked on a strip using an electrical method (U.S. Pat. No. 4,714,874) has been proposed.
However, these methods are methods that accurately adjust resistance, and must undergo a process of mass-producing the sensors first, measuring statistical characteristics of the sensors, and post-processing the measured information again using a method of adjusting the resistance marked on the sensors. However, the process of accurately adjusting the resistance, marked in large quantities, through the post-process is very inconvenient, and is difficult to use for practical application.
Methods in which colored marks are used to enable a spectral system capable of discriminating colors to use a colorimetric method (U.S. Pat. Nos. 3,907,503, 5,597,532, 6,168,957), and a method in which a plurality of color marks is read at various wavelengths of visible and infrared ray regions using a spectroscope (U.S. Pat. No. 5,945,341), and a method capable of reading bar codes (EP00075223B1, WO02088739A1) have been proposed. These methods using color or bar code are favorable for a calorimetric method-based sensor using the spectrum system, but they have technical and economic difficulties in being applied to the system using an electrochemical measurement mechanism. For example, the size and structure of a portion where the electrochemical sensor strip is inserted into the measuring device for the purpose of electrical connection, that is, a connection space of the sensor strip, is very limited in constructing a device and circuit for spectroscopically identifying a structure into which the production lot information is input. Further, a process of scattering and identifying various wavelengths of light detected by a detector is required to discriminate color, and a process of converting an analog signal into a digital signal and performing calculation is complicated, so that the device and its program are complicated, therefore the expense for constructing the system is greatly increased.
Furthermore, instead of the methods of marking the production lot information on the sensor strip, a method of recording information on a container or pack containing a sensor and allowing the information to be read by the measuring device (EP0880407B1) has been proposed. However, this method also has a possibility of causing the user to make an error of incorrectly reading a code recorded on the container.
For these reasons, the inventors of the present invention have conducted research into electrochemical biosensors in order to maintain economic efficiency in the construction of the measuring device while allowing the mass production of the electrochemical biosensor, which allows the production lot information thereof to be easily and accurately input into the measuring device without the mistake of the user and thus provides an accurate measurement value. In the process of the research, it has been found that, when the production lot information is recorded on the electrochemical biosensor strip using infrared absorption/reflection marks and when a production lot information identification portion at which the production lot information is recorded on the electrochemical biosensor strip is identified in the measuring device, there is no need to use a high-priced filter in the case where surface mounted miniaturized integrated infrared photo-reflector sensing devices in which light-emitting units (light emitters), that is, infrared emitting diodes, and light-receiving units (detectors), that is, photodiodes, are disposed in the same direction, are used in an integrated light-emitter and detector system in one component chip (hereafter called, photo-reflector), so that the light emitter-detector system has a simple construction on the same printed circuit board (PCB) of measuring device, and thus can not only reduce a complicated calculation process performed for post-treatment but also maintain economic efficiency in the construction of the measuring device. As a result, the present invention was completed.